Altered VDR-mediated transcriptional activity in prostate cancer stroma

Alejandro A. Hidalgo, Roberto Paredes, Victor M. Garcia, Geraldine Flynn, Candace S. Johnson, Donald L. Trump, Sergio A. Onate

Resultado de la investigación: Article

11 Citas (Scopus)

Resumen

The 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) mediated gene transcription in primary cultures of human prostate cells was analyzed using an adenoviral luciferase expression reporter under the control of the 25-hydroxy-vitamin D3-24-hydroxylase (CYP24) gene promoter. Stromal cells isolated from benign and malignant associated stroma (BAS and CAS) of a human clinical sample have been determined to contain similar levels of functional 1α,25(OH)2D3 receptor (VDR). However, VDR-mediated reporter activity of the luciferase reporter has been found to be limited 7-9-fold in CAS compared to 14-16-fold in BAS. Chromatin immunoprecipitation (ChIP) assays indicate that in the absence of added ligand VDR interact with the silencing mediator for retinoid and thyroid hormone (SMRT) corepressor in both cell types, with higher recruitment in CAS as compared to BAS cells. In the presence of added ligand, VDR in CAS cells exhibited decreased ligand-inducible DNA binding activity, altered recruitment of coregulators SRC-1 and CBP, and increased recruitment of SMRT corepressor, as compared to BAS. Additionally, overexpression of wild-type VDR recovered VDR-mediated transaction of CYP24 luciferase reporter. These results indicate that VDR structure/function and coregulator recruitment to 1α,25(OH)2D3 regulated genes is altered in the CaP stroma microenvironment.

Idioma originalEnglish
Páginas (desde-hasta)731-736
Número de páginas6
PublicaciónJournal of Steroid Biochemistry and Molecular Biology
Volumen103
N.º3-5
DOI
EstadoPublished - 1 mar 2007

Huella dactilar

Luciferases
Co-Repressor Proteins
Prostatic Neoplasms
Genes
Retinoids
Ligands
Thyroid Hormones
Personnel Selection
Transcription
Cell culture
Chromatin
Chromatin Immunoprecipitation
Assays
Stromal Cells
Prostate
DNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

Citar esto

Hidalgo, Alejandro A. ; Paredes, Roberto ; Garcia, Victor M. ; Flynn, Geraldine ; Johnson, Candace S. ; Trump, Donald L. ; Onate, Sergio A. / Altered VDR-mediated transcriptional activity in prostate cancer stroma. En: Journal of Steroid Biochemistry and Molecular Biology. 2007 ; Vol. 103, N.º 3-5. pp. 731-736.
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title = "Altered VDR-mediated transcriptional activity in prostate cancer stroma",
abstract = "The 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) mediated gene transcription in primary cultures of human prostate cells was analyzed using an adenoviral luciferase expression reporter under the control of the 25-hydroxy-vitamin D3-24-hydroxylase (CYP24) gene promoter. Stromal cells isolated from benign and malignant associated stroma (BAS and CAS) of a human clinical sample have been determined to contain similar levels of functional 1α,25(OH)2D3 receptor (VDR). However, VDR-mediated reporter activity of the luciferase reporter has been found to be limited 7-9-fold in CAS compared to 14-16-fold in BAS. Chromatin immunoprecipitation (ChIP) assays indicate that in the absence of added ligand VDR interact with the silencing mediator for retinoid and thyroid hormone (SMRT) corepressor in both cell types, with higher recruitment in CAS as compared to BAS cells. In the presence of added ligand, VDR in CAS cells exhibited decreased ligand-inducible DNA binding activity, altered recruitment of coregulators SRC-1 and CBP, and increased recruitment of SMRT corepressor, as compared to BAS. Additionally, overexpression of wild-type VDR recovered VDR-mediated transaction of CYP24 luciferase reporter. These results indicate that VDR structure/function and coregulator recruitment to 1α,25(OH)2D3 regulated genes is altered in the CaP stroma microenvironment.",
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Altered VDR-mediated transcriptional activity in prostate cancer stroma. / Hidalgo, Alejandro A.; Paredes, Roberto; Garcia, Victor M.; Flynn, Geraldine; Johnson, Candace S.; Trump, Donald L.; Onate, Sergio A.

En: Journal of Steroid Biochemistry and Molecular Biology, Vol. 103, N.º 3-5, 01.03.2007, p. 731-736.

Resultado de la investigación: Article

TY - JOUR

T1 - Altered VDR-mediated transcriptional activity in prostate cancer stroma

AU - Hidalgo, Alejandro A.

AU - Paredes, Roberto

AU - Garcia, Victor M.

AU - Flynn, Geraldine

AU - Johnson, Candace S.

AU - Trump, Donald L.

AU - Onate, Sergio A.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - The 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) mediated gene transcription in primary cultures of human prostate cells was analyzed using an adenoviral luciferase expression reporter under the control of the 25-hydroxy-vitamin D3-24-hydroxylase (CYP24) gene promoter. Stromal cells isolated from benign and malignant associated stroma (BAS and CAS) of a human clinical sample have been determined to contain similar levels of functional 1α,25(OH)2D3 receptor (VDR). However, VDR-mediated reporter activity of the luciferase reporter has been found to be limited 7-9-fold in CAS compared to 14-16-fold in BAS. Chromatin immunoprecipitation (ChIP) assays indicate that in the absence of added ligand VDR interact with the silencing mediator for retinoid and thyroid hormone (SMRT) corepressor in both cell types, with higher recruitment in CAS as compared to BAS cells. In the presence of added ligand, VDR in CAS cells exhibited decreased ligand-inducible DNA binding activity, altered recruitment of coregulators SRC-1 and CBP, and increased recruitment of SMRT corepressor, as compared to BAS. Additionally, overexpression of wild-type VDR recovered VDR-mediated transaction of CYP24 luciferase reporter. These results indicate that VDR structure/function and coregulator recruitment to 1α,25(OH)2D3 regulated genes is altered in the CaP stroma microenvironment.

AB - The 1α,25-dihydroxy-vitamin D3 (1α,25(OH)2D3) mediated gene transcription in primary cultures of human prostate cells was analyzed using an adenoviral luciferase expression reporter under the control of the 25-hydroxy-vitamin D3-24-hydroxylase (CYP24) gene promoter. Stromal cells isolated from benign and malignant associated stroma (BAS and CAS) of a human clinical sample have been determined to contain similar levels of functional 1α,25(OH)2D3 receptor (VDR). However, VDR-mediated reporter activity of the luciferase reporter has been found to be limited 7-9-fold in CAS compared to 14-16-fold in BAS. Chromatin immunoprecipitation (ChIP) assays indicate that in the absence of added ligand VDR interact with the silencing mediator for retinoid and thyroid hormone (SMRT) corepressor in both cell types, with higher recruitment in CAS as compared to BAS cells. In the presence of added ligand, VDR in CAS cells exhibited decreased ligand-inducible DNA binding activity, altered recruitment of coregulators SRC-1 and CBP, and increased recruitment of SMRT corepressor, as compared to BAS. Additionally, overexpression of wild-type VDR recovered VDR-mediated transaction of CYP24 luciferase reporter. These results indicate that VDR structure/function and coregulator recruitment to 1α,25(OH)2D3 regulated genes is altered in the CaP stroma microenvironment.

KW - Coactivator

KW - Corepressor

KW - Nuclear receptor

KW - Prostate cancer microenvironment

KW - Prostate cancer stromal cells

KW - Transcriptional regulation

KW - Vitamin D receptor

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U2 - 10.1016/j.jsbmb.2006.12.072

DO - 10.1016/j.jsbmb.2006.12.072

M3 - Article

C2 - 17368189

AN - SCOPUS:33947105057

VL - 103

SP - 731

EP - 736

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 3-5

ER -